Pathogenesis of epithelial-mesenchymal transition relating to progressing fibrosis and its clinical significance

上皮-间充质转化(EMT)是一种损伤的上皮细胞获得肌成纤维细胞特性，导致进行性纤维化的现象。分别对肾纤维化、胆管周围纤维化和皮肤纤维化中的肾上皮、胆管上皮和滤泡上皮进行EMT分析。在肾纤维化中获得了不完全肾再生的肌成纤维细胞特性；这种EMT被PGE2和NGAL抑制，但被骨桥蛋白促进。由于肾脏胚泡具有肌成纤维细胞特性，提示肾脏EMT是一种对肾脏胚泡的逆行现象。胆管周围纤维化的胆管上皮和皮肤纤维化的滤泡上皮均未见明显的EMT。肌成纤维细胞可能来源于间充质干细胞，如周细胞和骨髓干细胞。本研究提出了一个新的概念(EMT理论)，这将为顽固性纤维化的可能治疗提供线索。

Epithelial-mesenchymal transition (EMT) is a phenomenon in which injured epithelia acquire myofibroblastic properties, leading to progressive fibrosis. EMT was analyzed in renal epithelia, bile duct epithelia and follicular epithelia in renal fibrosis, peribiliary fibrosis and cutaneous fibrosis, respectively. The acquisition of myofibroblastic properties of incomplete renal regeneration in renal fibrosis was demonstrated; this EMT was inhibited by PGE2 and NGAL, but promoted by osteopontin. Since nephric blastema showed myofibroblastic properties, suggesting that renal EMT is a retroactive phenomenon towards renal blastema. Evident EMT was not shown in the bile duct epithelia in peribiliary fibrosis or follicular epithelia in cutaneous fibrosis. Myofibroblasts may be derived from the mesenchymal stem cells such as pericytes and bone-marrow stem cells. The present study gives a novel concept (EMT theory), which would open clues of possible therapies for intractable fibrosis.